Abstract
A series of potent 2-carboxychromone-based melanin-concentrating hormone receptor 1 (MCHr1) antagonists were synthesized and evaluated for hERG (human Ether-a-go-go Related Gene) channel affinity and functional blockade. Basic dialkylamine-terminated analogs were found to weakly bind the hERG channel and provided marked improvement in a functional patch-clamp assay versus previously reported antagonists of the series.
MeSH terms
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Amides / pharmacology*
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Animals
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Chromones / pharmacology*
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Ether-A-Go-Go Potassium Channels / drug effects
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Ether-A-Go-Go Potassium Channels / metabolism*
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Humans
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Inhibitory Concentration 50
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Mice
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Obesity / drug therapy
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Patch-Clamp Techniques
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Pharmacokinetics
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Receptors, Pituitary Hormone / antagonists & inhibitors*
Substances
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Amides
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Chromones
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Ether-A-Go-Go Potassium Channels
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Receptors, Pituitary Hormone
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melanin-concentrating hormone receptor